Takahashi Hidenori, Ishikawa Toshiaki, Ishiguro Megumi, Okazaki Satoshi, Mogushi Kaoru, Kobayashi Hirotoshi, Iida Satoru, Mizushima Hiroshi, Tanaka Hiroshi, Uetake Hiroyuki, Sugihara Kenichi
Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
Department of Translational Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan.
BMC Cancer. 2015 Oct 24;15:794. doi: 10.1186/s12885-015-1783-y.
The potential of expression profiling using microarray analysis as a tool to predict the prognosis for different types of cancer has been realized. This study aimed to identify a novel biomarker for colorectal cancer (CRC).
The expression profiles of cancer cells in 152 patients with stage I-III CRC were examined using microarray analysis. High expression in CRC cells, especially in patients with distant recurrences, was a prerequisite to select candidate genes. Thus, we identified seventeen candidate genes, and selected Traf2- and Nck-interacting kinase (TNIK), which was known to be associated with progression in CRC through Wnt signaling pathways. We analyzed the protein expression of TNIK using immunohistochemistry (IHC) and investigated the relationship between protein expression and patient characteristics in 220 stage I-III CRC patients.
Relapse-free survival was significantly worse in the TNIK high expression group than in the TNIK low expression group in stage II (p = 0.028) and stage III (p = 0.006) patients. In multivariate analysis, high TNIK expression was identified as a significant independent risk factor of distant recurrence in stage III patients.
This study is the first to demonstrate the prognostic significance of intratumoral TNIK protein expression in clinical tissue samples of CRC, in that high expression of TNIK protein in primary tumors was associated with distant recurrence in stage II and III CRC patients. This TNIK IHC study might contribute to practical decision-making in the treatment of these patients.
利用微阵列分析进行表达谱分析作为预测不同类型癌症预后的工具的潜力已得到认可。本研究旨在鉴定一种用于结直肠癌（CRC）的新型生物标志物。
使用微阵列分析检测了152例I - III期CRC患者癌细胞的表达谱。在CRC细胞中高表达，尤其是在远处复发患者中高表达，是选择候选基因的前提条件。因此，我们鉴定了17个候选基因，并选择了已知通过Wnt信号通路与CRC进展相关的Traf2和Nck相互作用激酶（TNIK）。我们使用免疫组织化学（IHC）分析了TNIK的蛋白表达，并研究了220例I - III期CRC患者中蛋白表达与患者特征之间的关系。
在II期（p = 0.028）和III期（p = 0.006）患者中，TNIK高表达组的无复发生存期明显比TNIK低表达组差。在多变量分析中，高TNIK表达被确定为III期患者远处复发的显著独立危险因素。
本研究首次证明了肿瘤内TNIK蛋白表达在CRC临床组织样本中的预后意义，即原发性肿瘤中TNIK蛋白的高表达与II期和III期CRC患者的远处复发相关。这项TNIK免疫组织化学研究可能有助于这些患者治疗中的实际决策。
